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Clinical Trial VICCPHI1360


A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination with Chemotherapy in Subjects with Advanced Solid Tumors

Principal Investigator(s)

Jordan Berlin


  • Protocol No. VICCPHI1360
  • Open Date: 04/22/2014
  • Staging: Phase I
  • Age Group: Adults
  • Scope: National
  • Objective: To determine the MTD of GS-5745 monotherapy in subjects with advanced solid tumors.
  • Disease Sites: Pancreatic; Esophageal; Lung; Non Small Cell; Gastric/Gastroesophageal
  • Therapies: Chemotherapy - cytotoxic; Molecular Targeted Agents / Immunotherapy / Biologics; Supportive Care
  • Drugs: Alimta; Carboplatin; GS-5745; Gemcitabine; Nab-paclitaxel; Paclitaxel; Pemetrexed; mFOLFOX6
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT01803282
  • Secondary Protocol No: GS-US-296-0101


Patients are being asked to take part in this research study because they have not previously received chemotherapy, and have one of the following types of advanced cancer: Pancreas, Stomach, Esophagogastric (junction of the stomach and esophagus), or Lung. Patients are being invited to take part in a research study to test an investigational drug called GS-5745. "Investigational" means GS-5745 has not been approved by the United States Food and Drug Administration (FDA) or any government for doctors to prescribe to patients. GS-5745 is made by the company Gilead Sciences, Inc. Gilead is the sponsor of this study, and is paying Vanderbilt to conduct the study. GS-5745 is a liquid given by an intravenous (IV) infusion (using a needle into a vein) over approximately 30 minutes. This is the first study in which GS-5745 is being given to humans so the risks in humans are not known. We are doing this research study to find a dose of GS-5745 that would be safe in humans. Future studies (called Phase II studies) can then test whether or not GS-5745 is useful against cancer. The purpose of this study is to find answers to the following research questions: 1. What is the highest dose of GS-5745 that can safely be given to patients when given every 2 or 3 weeks- 2. What are the side effects of GS-5745 when given alone and when given in combination with chemotherapy- 3. How much GS-5745 is in the blood at specific times after dosing and how does the body get rid of GS-5745- 4. What are possible reasons why certain people respond to treatments and why do certain types of cancer worsen-


Ages Eligible for Study:18 Years and older
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No


Inclusion Criteria:
1. Male or female > 18 years of age
2. Part A: histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
3. Part B Pancreatic Adenocarcinoma:
a. Presence of histologically confirmed inoperable locally advanced or metastatic pancreatic adenocarcinoma
4. Part B NSCLC:
1. Stage IIIB with malignant pleural effusion/pleural seeding or stage IV histologically confirmed NSCLC
2. Absence of known epidermal growth factor receptor (EGFR) mutation
3. Absence of known translocation or inversion events involving the ALK gene locus (resulting in EML4-ALK fusion)
5. Part B Esophagogastric Adenocarcinoma:
1. Histologically confirmed inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastrooesophageal junction) or relapsed gastric adenocarcinoma
2. Human epidermal growth factor receptor 2 (HER2)-negative tumor (primary tumor or metastatic lesion)
6. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of study drug dosing (with the exception of alopecia [Grade 1 or 2 permitted] and neurotoxicity [Grade 1 or 2 permitted])
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
8. Life expectancy of > 3 months in the opinion of the Investigator
9. Adequate organ function defined as follows:
1. Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
2. Hepatic: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN
3. Renal: Serum Creatinine ≤ 1.5 x ULN
10. Coagulation: international normalized ratio (INR) ≤ 1.6 (unless receiving anticoagulation therapy). Subjects on full-dose oral anticoagulation must be on a stable dose (minimum duration 14 days). If receiving warfarin, the subject must have an INR ≤ 3.0 and no active bleeding (ie, no bleeding within 14 days prior to first dose of study drug). Subjects on low molecular weight heparin will be allowed.
11. For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for 90 days following the last dose of study drugs. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional postmenopausal range and a negative serum or urine Beta-HCG), or is menopausal (age > 55 years with amenorrhea for > 6 months).
12. For male subjects of childbearing potential having intercourse with females of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of study drug, throughout the study treatment period, and for 90 days following the last dose of study drugs, and to refrain from sperm donation from the start of study drug, throughout the study treatment period, and for 90 days following the last dose of study drugs. Note: A male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy, or has ongoing testicular suppression with a depot luteinizing hormone releasing hormone (LH RH) agonist (eg, goserelin acetate [Zoladex®]), leuprolide acetate [Lupron®]), or triptorelin pamoate [Trelstar®]).
13. Willingness to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions
14. Evidence of a signed informed consent form
Exclusion Criteria:
1. History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the Investigator and Medical Monitor would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion
2. Pregnant or lactating
3. Subject with known central nervous system (CNS) metastases, unless metastases are treated and stable and the subject does not require systemic steroids
4. For Part B, small cell lung cancer
5. For Part B, diagnosis of pancreatic islet cell neoplasm
6. For Part B, subjects who have received prior cytotoxic chemotherapy to treat their metastatic disease
7. Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of study Day 1
8. History of major surgery within 28 days prior to enrollment
9. Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires IV antibiotics
10. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 28 days or 5 half-lives, whichever is shorter, of study drug dosing (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t½ > 10 days); concurrent use of hormone therapy for breast or prostate cancer is permitted
11. Clinically significant bleeding within 28 days of Day 1
12. Subjects known to be positive for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B